Mycobacterium tuberculosis (Mtb) infects about one third of the population worldwide. An estimated 8 million new cases and 2 million deaths occur annually placing tuberculosis as a significant health problem. The adaptive cellular immune response is essential in the host control of tuberculosis. However, many of the innate immune mechanisms that are required to result in an optimal acquired cellular immune response to Mycobacterium tuberculosis remain to be characterized; a better understanding of this link is critical in the development of an effective vaccine. We have identified a thymocyte population from humans that recognizes Mtb-infected antigen-presenting cells. This proposal is designed to 1) address the hypothesis that the Mtb-reactive thymocytes are an aspect of the innate immune response 2) identify the functional effector mechanisms associated with this population 3) characterize the antigen processing and presentation pathway used for recognition by Mtb-reactive thymocytes. [unreadable] [unreadable] [unreadable]